This study was designed to determine the feasibility of administering high dose intensive chemotherapy for patients with advanced diffuse histiocytic lymphomas using measures to prevent infection. Patients with diffuse histiocytic lymphoma who are found to be stage III or IV after appropriate staging techniques have been placed in reverse isolation in a laminar air flow unit and have begun all non-absorbable antibioties. They are then treated with high dose chemotherapy with cyclophosphamide 1500 mg/sq.m IV day one, adriamycin 60 mg/sq.m IV day one, vincristine 1.4 mg/sq.m IV days one and eight and a ten day courses of oral prednisone at 40 mg/sq.m. Eight patients have been entered to date. Myelosuppression has been the most frequently noted toxicity and though often severe has been brief. Results to date show four complete responses, one partial response and three failures. There have been three deaths of those patients achieving complete response, however. One patient died from adriamycin cardiotoxicity, one from disseminated fungemia and one patient with renal failure. The patient who has achieved a partial remisson is still under therapy. Although the results of this study indicate that high dose chemotherapy with these agents is effective at achieving complete responses, further study is necessary to determine if such aggressive therapy is warranted.